{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:29:12Z","timestamp":1740169752395,"version":"3.37.3"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T00:00:00Z","timestamp":1527552000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Autonomic Government of Galicia","award":["GRC 2013\/061"],"award-info":[{"award-number":["GRC 2013\/061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2018,5,29]]},"abstract":"<jats:p>Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (<jats:italic>FBN1<\/jats:italic>) gene. We, by using targeted next-generation sequence analysis, identified a novel intronic<jats:italic> FBN1<\/jats:italic> mutation (the c.2678-15C&gt;A variant) in a MFS patient with aortic dilatation. The computational predictions showed that the heterozygous c.2678-15C&gt;A intronic variant might influence the splicing process by differentially affecting canonical versus cryptic splice site utilization within intron 22 of the<jats:italic> FBN1<\/jats:italic> gene. RT-PCR and Western blot analyses, using<jats:italic> FBN1<\/jats:italic> minigenes transfected into HeLa and COS-7 cells, revealed that the c.2678-15C&gt;A variant disrupts normal splicing of intron 22 leading to aberrant 13-nt intron 22 inclusion, frameshift, and premature termination codon. Collectively, the results strongly suggest that the c.2678-15C&gt;A variant could lead to haploinsufficiency of the FBN1 functional protein and structural connective tissue fragility in MFS complicated by aorta dilation, a finding that further expands on the genetic basis of aortic pathology.<\/jats:p>","DOI":"10.1155\/2018\/3536495","type":"journal-article","created":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T19:30:50Z","timestamp":1527622250000},"page":"1-10","source":"Crossref","is-referenced-by-count":11,"title":["A Novel Heterozygous Intronic Mutation in the<i> FBN1<\/i> Gene Contributes to<i> FBN1<\/i> RNA Missplicing Events in the Marfan Syndrome"],"prefix":"10.1155","volume":"2018","author":[{"given":"Mario","family":"Torrado","sequence":"first","affiliation":[{"name":"Institute of Health Sciences, University of A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Maneiro","sequence":"additional","affiliation":[{"name":"Health in Code, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pablo","family":"Trujillo-Quintero","sequence":"additional","affiliation":[{"name":"Health in Code, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital General Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-4113","authenticated-orcid":true,"given":"Alexander T.","family":"Mikhailov","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, University of A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Monserrat","sequence":"additional","affiliation":[{"name":"Health in Code, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2011.02.004"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1171"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.07.004"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12436"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.30"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.039669"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.42"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2014.950223"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.03.423"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.07.033"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1086\/520125"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2015.04.002"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.91"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22540"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0334-7"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100573"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0260-4"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.072366mt"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026392"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx360"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380110112"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1566807"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2018\/3536495.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2018\/3536495.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2018\/3536495.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T19:30:57Z","timestamp":1527622257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/bmri\/2018\/3536495\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,29]]},"references-count":23,"alternative-id":["3536495","3536495"],"URL":"https:\/\/doi.org\/10.1155\/2018\/3536495","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"type":"print","value":"2314-6133"},{"type":"electronic","value":"2314-6141"}],"subject":[],"published":{"date-parts":[[2018,5,29]]}}}